Metaxalone and Protriptyline interaction

Metaxalone and Protriptyline: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Metaxalone label · effective 2026-02-03

Major

If concomitant use with another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of metaxalone and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases.

Warnings and precautionsby drug classView label on DailyMed
Major

Serotonin syndrome has resulted from concomitant use of metaxalone (within the recommended dosage range) and other serotonergic drugs [see Warnings and Precautions (5.1) ].

Drug interactionsby drug classView label on DailyMed
Major

Depressants If concomitant use of Metaxalone Tablets, 640 mg and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage modification.

Drug interactionsby drug classView label on DailyMed
Major

Due to the additive pharmacologic effect, concomitant use of Metaxalone Tablets, 640 mg with other CNS depressants may increase the risk of sedation and respiratory depression [see Warnings and Precautions (5.2) ].

Drug interactionsby drug classView label on DailyMed

From the Protriptyline (Protriptyline Hydrochloride) label · effective 2023-07-25

Moderate

Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.